K Liang*, G Pratx, R Manjappa, B Ha, C Liu, S Melemenidis, J Rao, B Loo, Stanford University, Stanford, CA

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  K Liang

WE-D-BRA-4 (Wednesday, 7/13/2022) 10:15 AM - 11:15 AM [Eastern Time (GMT-4)]

Ballroom A

Purpose: To develop real-time optical oximetry under FLASH radiotherapy (FLASH-RT) and conventional radiotherapy, and further understand the normal tissue-sparing effect of FLASH-RT.

Methods: An epifluorescent laser system was constructed to measure the kinetics of O₂ depletion during FLASH-RT with high temporal resolution. A 1 kHz 640 nm laser excites air-tight samples of PBS buffer containing a soluble oxygen-sensitive phosphorescent nanoprobe and various concentrations of oxygen. The same optic fibre detects the 794 nm phosphorescent decay of the nanoprobe. The decay lifetime is calculated by averaging the decays of several pulses, and fitting the data to a dual-exponential function. Calibration measurements with unirradiated samples ranging from 0-100 μM [O] are used to determine the relationship between [O] and probe lifetime (via a Stern-Volmer plot). Validation of this method includes comparing the calculated and known [O] of the calibration samples. Approximately 20 Gy of CONV-RT and FLASH-RT are then repeatedly delivered to separate samples to detect the change in oxygen concentration.

Results: Examination of [O₂] under CONV-RT exhibited a linear decrease in concentration over time during irradiation. The measured O₂ depletion yield agrees with previous measurements made using a polarographic electrode. Under FLASH-RT, [O] exhibited a significantly steeper decrease during irradiation, and an overall 43% +/- 40% smaller yield of depletion. The error bars are absolute, and represent the 95% confidence intervals. To achieve better temporal resolution, a smaller number of decays are combined resulting in significantly wider confidence intervals and decreased SNR. Due to the properties of the nanoprobe, the rate of depletion is most accurately measured when [O] is below 40 μM.

Conclusion: This work supports the potential to measure oxygen levels during FLASH irradiation in-vivo. A greater biochemical understanding of FLASH-RT would be crucial to effective translation of this new treatment to clinical use.

Funding Support, Disclosures, and Conflict of Interest: Billy W. Loo Jr. : TibaRay (founder and board member), Varian Medical Systems (research support)

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